Due to the completion of the human and mouse genomes as well as advances in mouse technologies, there has been an enormous increase in the number of mouse mutants and models for human disease. Maintaining and distributing pathogen-free mouse strains is both labor-intensive and costly for individual investigators to sustain long term. The NIH/NCRR recognized the need for a common repository and distribution center for genetically modified mice and in 1999 they responded by funding the Mutant Mouse Regional Resource Centers (MMRRC). UNC-Chapel Hill is one of three MMRRC centers that has been developing this resource for the benefit of the entire biomedical community. Since initial funding began in 1999 and was renewed in 2005, a significant amount of effort has been invested in creating the organizational infrastructure and establishing standard operating procedures (SOPs) for importation, rederivation, phenotyping, cryopreservation and distribution of mutant mouse strains. In 2001, the MMRRC-UNC accepted the first strain and as of 2009,1639 strains have been archived by the three centers and are available for distribution. In parallel with these efforts, the MMRRC-UNC has also taken advantage of the expertise available at UNC to bring new technologies and resources to the community such as mutant ES-cell lines, mutant gnotobiotic strains, and improved in vitro fertilization methods. To meet future demands for MMRRC services and improve upon existing technologies, this proposal aims to: (1) Streamline procedures to import, archive and distribute genetically modified mouse strains, (2) Investigate the mechanisms of oxidative damage in cryopreserved mouse sperm, and (3) archive and integrate Collaborative Cross mice as an MMRRC collection. PUBLIC HEALTH RELEVANCE (provided by applicant): In order to improve our understanding of human disease susceptibility and the implications this has for medicine, research must focus on gene function by inducing mouse mutations and then studying the resulting cellular or physiological abnormalities. The MMRRC imports, archives and distributes these important mutant strains to the scientific community for addressing the genetics underlying human disease conditions.